1. Field of the Invention
The present invention relates to an active retinal implant to be implanted into an eye, with an array of stimulation elements that emit stimulation signals to cells of the retina.
2. Related Prior Art
By way of example, such a retinal implant has been disclosed in WO 2005/000395 A1.
The known retinal implant serves to counteract a loss of vision due to degenerations of the retina. Here, the basic idea is to implant into the eye of a patient a microelectronic stimulation chip that replaces the lost vision by electrical excitation of neurons.
In doing so, there are two different approaches as to how such retinal prostheses can be designed.
The subretinal approach described in WO 2005/000395 A1, mentioned at the outset, and in e.g. EP 0 460 320 A2 uses a stimulation chip, implanted into the subretinal space between the outer retina and the pigment epithelium of the retina, that converts ambient light, impinging on an array of photodiodes integrated in the stimulation chip, into electrical stimulation signals for neurons. These stimulation signals actuate an array of stimulation electrodes, which stimulate the neurons of the retina with spatially resolved electrical stimulation signals corresponding to the image information “seen” by the array of photodiodes.
Thus, this retinal implant stimulates the remaining, intact neurons of the degenerated retina, that is to say horizontal cells, bipolar cells, amacrine cells and possibly ganglion cells as well. The visual image incident on the array of photodiodes or more-complex elements is, in the process, on the stimulation chip converted into an electrical stimulation pattern. This stimulation pattern then leads to the electrical stimulation of neurons, by means of which the stimulation is then guided to the ganglion cells in the inner retina and, from there, led into the visual cortex via the optic nerve. In other words, the subretinal approach utilizes the natural interconnection of the previously present and now degenerated or lost photoreceptors with the ganglion cells in order to supply the visual cortex with nerve impulses, which correspond to the seen image, in a conventional fashion. Thus, the known implant is a replacement for the lost photoreceptors and it, like the latter, converts image information into electrical stimulation patterns.
In contrast thereto, the epiretinal approach utilizes a device, consisting of an extra-ocular and an intra-ocular part, which communicate with one another in a suitable fashion. The extra-ocular part comprises a camera and a microelectronic circuit for coding captured light, that is to say the image information, and transmitting it to the intra-ocular part as a stimulation pattern. The intra-ocular part comprises an array of stimulation electrodes, which contacts neurons of the inner retina and thus directly electrically stimulates the ganglion cells situated there.
A large number of publications disclose that the transmission of the electrical stimulation signals from the stimulation electrodes to the contacted cells, required in these implants, requires particular attention. This is because the coupling between a stimulation electrode and the contacted tissue is capacitive and so only transient signals can be used for electrical stimulation. This capacitive coupling is based on the fact that a capacitance (Helmholtz double layer) is formed in the eye at the boundary between the electrode and electrolyte as a result of the electrode polarization. Against this background, the stimulation signals are transmitted as pulses.
In the subretinal implant as per WO 2005/000395, mentioned at the outset, the incident light is therefore converted into voltage pulses with a pulse length of approximately 500 microseconds and a pulse spacing of preferably 50 milliseconds, such that a repetition frequency of 20 Hz results, which was found to be sufficient for flicker-free vision. In doing so, the pulse spacing moreover is sufficient to restore the electrode polarization completely.
WO 2007/128404 A1 deals with the question as to how the perception can be further improved by a suitable choice of pulse length and repetition frequency of the electrical stimulation signals. Starting from experimental findings using implanted subretinal implants, it proposes to subdivide the multiplicity of stimulation electrodes into at least two groups of stimulation electrodes, which are actuated over time, one after another, in order to emit stimulation signals.
Thus, the seen image is not imaged as a whole on the stimulation electrodes with a high repetition frequency; rather, the image is decomposed, so to speak, into at least two partial images, which are alternately “switched-through” at a lower repetition frequency to the stimulation electrodes.
By way of example, if four partial images, each with a repetition frequency of 5 Hz, are emitted as stimulation signals from, in each case, a quarter of the stimulation electrodes, a new (partial) image in the form of stimulation signals, that is to say pulses, is nevertheless emitted to the cells of the retina by the stimulation electrodes, respectively with a partial image frequency of 20 Hz.
This may slightly reduce the spatial resolution, but the image repetition frequency of 20 Hz required for physiologically flicker-free vision is achieved.
Depending on the number and local “density” of the stimulation electrodes, it is also possible to use a larger number of partial images in the process, provided that the desired spatial resolution is achieved as a result of this. In the case of a larger number of partial images, the repetition frequency of the individual partial images can then be further reduced, wherein, nevertheless, a new partial image in the form of a pattern of stimulation pulses is emitted every 50 milliseconds, i.e. with an image repetition frequency of 20 Hz.
A further problem in the known retinal implants is the energy supply of the stimulation chip.
That is to say, the energy for generating the electrical stimulation signals cannot be obtained from the incident useful light itself, even in subretinal implants, and so additional external energy is required. Here, this external energy is either obtained from additional invisible light irradiated into the eye, coupled in from the outside by means of e.g. a coil, or conducted by a wire led into the eye.
The implant known from WO 2005/000395 A1 is supplied with electrical energy, without the need for wires, by irradiated IR light or inductively coupled RF energy, wherein information for controlling the implant may be contained in this external energy supplied from the outside.
However, since wireless retinal implants for human applications that have a satisfactory quality are not currently available, at the moment use is made of not only epiretinal but also subretinal implants, which are supplied with the required external energy by wires.
WO 2007/121901 A1 describes e.g. a subretinal retinal implant, in which the external energy and control signals are guided by a wire to the stimulation chip implanted in the eye. Here, the wire is applied and fixed to the sclera of the eye in order to avoid forces on the implant.
Since, on the one hand, integrated circuits operated with DC voltage are generally available on the implants and, on the other hand, there is little space on the implants themselves, most known implants are directly supplied with DC voltage. That is to say that, in the case of AC voltage supply, the rectifiers required on the implant would need too much space and also could not be implemented in integrated circuits in a technically expedient fashion, in particular due to the required smoothing capacitors.
However, in the long run, the wired transmission of DC voltage leads to electrolytic decomposition processes in the tissue surrounding the wire and so this method of supplying implants with external energy is also unsatisfactory.
Therefore, WO 2008/037362 A2 proposes to supply the implant with at least one substantially rectangular electrical AC voltage that, averaged over time, is at least almost without a DC voltage component in relation to the tissue mass. In the process, the potential level can be selected such that, averaged over time, the supply voltage is at least almost without a DC voltage component. This, at least to a large extent, avoids the bothersome electrolytic decomposition processes.
Despite the above-described promising approaches for solving the substantial technological problems in the context of epiretinal and, in particular, subretinal retinal implants, the currently available retinal implants do not yet satisfy possibly all requirements for comprehensive and satisfactory patient care.
Furthermore, it still remains to be investigated whether the epiretinal and/or subretinal approach is suitable for all patients suffering from visual impairment as a result of losing their natural photoreceptors, as is the case in retinits pigmentosa or in age-dependent macular degeneration.
U.S. Pat. No. 5,836,996A discloses a different retinal implant approach using a first layer of photodiodes that convert incident ambient light into electrical signals. These electrical signals control light emitting elements that emit optical signals that are received by a second layer of photodiodes. These second photodiodes convert the optical signals into electrical stimulation signals that are used to stimulate cells of the retina.
By this, an optical attenuator is provided that ensures that the level of the electrical stimulation signals is not such that they damage the retina. It is also disclosed to use only one layer of photodiodes that directly emit electrical stimulation asignals to retinal cells.
A recently expanding alternative to implanting a retinal implant of the type described thus far consists of a genetic treatment of patients suffering from a loss of their natural photoreceptors. In this approach, using genetic-engineering methods, light sensitive cytoplasmic channels are introduced into the still-present neurons of blind or visually impaired people, such that the electrical activity of the neurons can be modulated by irradiation with light, which causes a perception of light.
This approach is based on reports from different scientific groups, who used different derivatives of rhodopsin, usually found in bacteria, to control, by irradiation with light, ion channels in the cytoplasmic membrane of neurons in respect of the opening probability thereof. The transmembrane ion channels modified in this fashion could be introduced into different cell types of the retina, such as ganglion cells and bipolar cells, in which the modulation of the electrical activity leads to light perception in the visual centres.
In doing so, also rhodopsin derivatives with different spectral sensitivity were used for generating channels, which, introduced into ON bipolar cells or OFF bipolar cells by transgenic techniques, permit a separate actuation of the brightness coding ON bipolar cells and the darkness coding OFF bipolar cells as a result of different spectral light stimulation.
However, the light intensity required in order to be able to use light to modulate the electrical activity of neurons equipped with these rhodopsin-controlled channels is several orders of magnitudes greater than the light intensity required for the activation of the natural photoreceptors, i.e. the rods and cones; see Lagali et al.: “Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration”, Nature Neuroscience, volume 11, number 6, June 2008, pages 667-675, with further references therein.
Lagali et al. report that when using neuromodulators, genetically coded in this fashion, in ON bipolar cells at a light intensity of at least 1015 photons cm−2 s−1, light perception was noted in the ON path of the retina even when photoreceptors were absent. It should be noted at this point that 2.5×1015 photons cm−2 s−1 at 500 nm correspond to approximately 1 mW cm−2.
Comparable values were determined for ganglion cells. By contrast, the minimum intensities for rods and cones are only 106 photons cm−2 s−1 and 1010 photons cm−2s−1, respectively.
Even if it seems possible to increase the light sensitivity of rhodopsin-controlled channels by up to three orders of magnitude, the sensitivity of the rods and cones will not be achievable under any circumstances, not even approximately, because the other cells of the retina, which are made light sensitive by rhodopsin, lack the particular amplifying mechanisms of the rods and cones.